Compounds containing the butenolide ring which has the basic formula: ##STR1## occur widely in nature and often possess an unusual range of biological activities. They appear throughout the plant kingdom from the simple metabolites of lichens, mold and fungi, to the more complex sesquiterpenes of the family Compositae and steriodal glycosides of the families Ranunculaceae, Liliaceae, Scrophulariaceae, and Apocyanaceae. More recently butenolides have been observed in such diverse animal species as sponges, and insects. In the latter species they may play a significant role as chemical defense weapons.
Certain butenolide ring containing compounds are useful as insecticides, herbicides, and seed and plant growth regulators. Of considerable importance also is the widespread characteristic among butenolide containing compounds of allergenic, antibacterial, and antifungal activity.
Undoubtedly, Vitamin C is the most physiologically important butenolide ring containing compound. Other uses for certain butenolide ring containing compounds include recently reported uses of cardiac glycosides as having the unusual characteristics of reducing the frequency of the heartbeat but increasing the amplitude of the heartbeat.
The unusual range of usefulness of compounds containing the basic butenolide ring has stimulated considerable research on the synthesis of these valuable compounds. While numerous methods have been reported in the literature for the preparation for butenolides, see for example, Y. S. Rao, Chem. Rev., 64, 353 (1964); W. E. Epstein and A. C. Sonntag, J. Org. Chem., 32, 3390 (1967); K. Iwai, M. Kawai, H. Kosugi and H. Uda, Chem. Lett., 385 (1974); and K. Iwai, H. Kosugi and H. Uda, Chem. Lett., 1237 (1974), these methods all generally suffer from several disadvantages. Some of these disadvantages include inaccessibility of the starting materials, the necessity for employing severe reaction conditions, the very low yields of product obtained, and generally limited versatility in preparing the desired butenolide ring containing compounds.
Accordingly, one object of this invention is to provide a general synthesis route which has universal application for preparing a wide variety of butenolide ring containing compounds.
Another object of this invention is to provide a synthesis method for butenolide ring containing compounds which involves only a two-step synthesis and avoids the utilization of hydrogenation, Grignard reagents and other techniques often utilized by prior art synthesis methods.
Another object of this invention is to provide the compound .beta.-chlorobutenolide and gamma substituted derivatives thereof.
Yet another object of this invention is to provide .beta.-halobutenolides and gamma derivatives thereof, in unusually high yields, generally in excess of 90%.
Still another object is to replace the .beta. halogen of .beta.-halobutenolides to obtain .beta. alkyl, aryl and vinyl butenolides.